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Review
. 2025 Jul;32(1):201.
doi: 10.3892/mmr.2025.13566. Epub 2025 May 16.

Zinc in psychosis (Review)

Affiliations
Review

Zinc in psychosis (Review)

Christos Theleritis et al. Mol Med Rep. 2025 Jul.

Abstract

Zinc (Zn) may be associated with schizophrenia (SCH), since its altered homeostasis can contribute to abnormal glutamatergic neurotransmission, inflammation, neurodegeneration and autoimmune abnormalities. It has been proposed that a number of patients with SCH could benefit from the use of Zn, either on its own or along with vitamins C, E and B6, and prenatal supplementation of Zn during the gestation period can mitigate the lipopolysaccharide‑induced rat model of maternal immune activation. The aim of the present review was to summarize the various effects of Zn dyshomeostasis on patients with psychosis and to clarify in what ways they could benefit from Zn supplementation.

Keywords: psychosis; schizophrenia; zinc; zinc homeostasis.

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Conflict of interest statement

DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Schematic representation of the inhibitory effects of Zn on NMDARs. (A) High-affinity binding of Zn to the GluN2A subunit of NMDAR causes allosteric inhibition and attenuates channel opening. (B) Low-affinity binding of Zn to pore-lining residues of the NMDAR blocks the channel. Zn deficiency and disrupted Zn transport dynamics (e.g., in the presence of SLC39 gene mutations) could account for abnormal NMDAR function and altered glutamatergic neurotransmission in schizophrenia. The model of NMDAR hypofunction and the consequent inability to downregulate prefrontal glutamatergic neurons is widely accepted by researchers and clinicians, especially since the induction of schizophrenia-like symptoms has been detected following the administration of ketamine and phencyclidine in healthy subjects. Created in BioRender. Stefanou, M. (2025) https://BioRender.com/mcf93wr. NMDAR, NMDA receptor; Zn, zinc.

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